Osteoporotic fractures and myopathies are disabling consequences of chronic glucocorticoid (GC) therapy. In vitro and in vivo, GCs inhibit osteoblast production of insulin-like growth factor I(IGF-I), a hormone known to promote collagen synthesis and cell replication in bone. GC therapy may also interfere with systemic action of IGF-I by increasing levels of a circulating IGF-I inhibitor. Negative GC effects on IGF-I production and action, therefore, appear to be important mechanisms by which GCs induce osteoporosis. Furthermore, GC therapy often results in muscle atrophy and weakness. IGF-I has been shown to have anabolic effects on skeletal muscle and may prevent the catabolic changes induced by GCs. The proposed studies will investigate the pathophysiology of GC effects upon bone and muscle and determine whether administration of IGF- I/BP-3 may prevent GC-induced osteoporosis and myopathy.